The show focuses on George and Louise Jefferson, a prosperous African-American couple who have been able to move from Queens to Manhattan owing to the success of George's dry-cleaning chain, Jefferson Cleaners. The show was launched as the second (and longest running) spin-off of All in the Family, on which the Jeffersons had been the neighbors of Archie and Edith Bunker. The show was the creation of Norman Lear.  The Jeffersons eventually evolved into more of a traditional sitcom, but episodes occasionally focused on serious issues such as alcoholism, racism, suicide, gun control, being transgender, the KKK, and adult illiteracy. The epithets nigger and honky were used occasionally, especially during the earlier seasons.

The Jeffersons had one spin-off, titled Checking In. The series was centered on the Jeffersons' housekeeper, Florence, who takes a job as cleaning management at a hotel. Checking In lasted only four episodes, after which Florence returned to The Jeffersons with the story that the hotel had burned down in a fire. The Jeffersons also shared continuity with the sitcom E/R, which featured Lynne Moody who made a guest appearance in one episode of The Jeffersons. Sherman Hemsley guest-starred as George in two episodes of the series, which lasted for one season. The cancellation of The Jeffersons cleared the way for Marla Gibbs, who played Florence Johnston on the series, to move on to the NBC sitcom 227 in the fall of 1985, a year earlier than scheduled.

The Jeffersons ended in controversy after CBS abruptly canceled the series without allowing for a proper series finale. The cast was not informed until after the July 2, 1985, episode, "Red Robins"; actor Sherman Hemsley, who portrayed George Jefferson, said he learned that the show was canceled by reading it in the newspaper. Isabel Sanford (Louise Jefferson), who heard about the cancellation through her cousin who read it in the tabloids, has publicly stated that she found the cancellation with no proper finale to be disrespectful on the network's part. Per an article in the May 8, 1985, Los Angeles Times, the series was cancelled by announcement at the CBS network "upfront" presentation the day before, nearly two months before the airing of the final episode. Actor Franklin Cover, who played Tom Willis, also heard about the cancellation while watching Entertainment Tonight.

The cast reunited in a stage play based on the sitcom. In season 5 episode 17 of The Fresh Prince of Bel-Air, titled "Will Is from Mars" (1995), the Jeffersons made a guest appearance as a couple in therapy class. In the 1996 series finale of The Fresh Prince of Bel-Air, the Jeffersons made a guest appearance as the buyers of the Banks family house. In an episode of Tyler Perry's House of Payne in 2011, Sherman Hemsley and Marla Gibbs reprised their roles of George Jefferson and Florence Johnston.

In 1985, Hemsley and Sanford made a special joint guest appearance in the Canale 5 comedy show Grand Hotel, starring the Italian actors Paolo Villaggio, the comic duo Franco & Ciccio, and Carmen Russo. They were guests in the fictional hotel and their voices were dubbed by Italian actors Enzo Garinei (George) and Isa di Marzio (Louise), who also dubbed their characters for the full series. As of 2022, the members still alive from the main cast include Marla Gibbs, Berlinda Tolbert, and Damon Evans.